Gonorrhea (GC) and chlamydia (CT) at the pharynx and the rectum comprise the majority of GC and CT infections in men who have sex with men (MSM). However, as primarily asymptomatic infections, they often go undiagnosed and untreated. As such, GC/CT infections at these extra-genital sites may constitute an important reservoir of sustained transmission in the MSM population. Gonococcal infections at the pharynx may also play an important role in fostering the development of antimicrobial resistance due to the unique constellation of Neisseria gonorrhoeae's ability to scavenge DNA and the oropharynx as important environment for commensal Neisseria species. Rectal GC/CT infections have been shown to increase the risk for HIV acquisition. However, little is known about the natural history of extra-genital GC and CT, nor the extent to which rectal GC/CT increase the risk of HIV acquisition through a biologically-mediated process or sexual behavior. This K23 proposal aims to 1) determine the natural history extra-genital gonorrhea and chlamydia infection among MSM & associated sociobehavioral determinants, and 2) quantify variations in HIV shedding at the rectum during rectal GC/CT infection by conducting a prospective cohort study of MSM, half of which are HIV-infected, who will self-collect pharyngeal and rectal swabs and document sexual activity on a weekly basis for one year. We will document incidence, duration of infection, and associated sociobehavioral factors with extra-genital GC/CT; and we will evaluate differences in HIV RNA log copies between baseline and incident rectal infections as well as describe temporal variations in HIV RNA shedding over the course of rectal GC/CT infections. We will also 3) test whether the risk of HIV acquisition is associated with rectal GC or CT infection controlling for seroadaptive behaviors using more than 10 years of clinical data collected at an urban STD Clinic; and 4) estimate the potential impact of enhanced extra-genital testing and treating on the incidence of GC, CT and HIV using deterministic mathematical modeling. Not only will these studies answer key clinical and epidemiologic question about extra-genital GC, CT and HIV, but these studies will provide experiential learning to complement a structured career development plan for the PI to develop skills in longitudinal data analysis, sociobehavioral research and mathematical modeling. The ultimate goal of this K23 award is to provide the time, experience, training and mentorship necessary to allow the PI to become an independent investigator dedicated to the prevention and control of STD and HIV in vulnerable populations.